Hoth Therapeutics Reveals GDNF’s Superior Efficacy in Obesity Treatment

Hoth Therapeutics, Inc. has announced promising results from its recent study, demonstrating that its glial cell-derived neurotrophic factor (GDNF) significantly outperforms semaglutide—an active ingredient in popular weight-loss medications such as Wegovy® and Ozempic®—in managing obesity and related metabolic conditions. The findings, released on February 10, 2026, highlight GDNF’s potential to transform treatment paradigms in a market valued at approximately $200 billion.

The preclinical study, conducted with support from the United States Veterans Administration, compared the efficacy of GDNF to semaglutide across multiple metrics, including weight management, glucose tolerance, and liver health. Notably, the results revealed that GDNF not only stabilized weight in female mouse models on a high-fat diet but also demonstrated significant improvements in glucose metabolism and reduced liver weight.

Key Findings from the Study

The research, which took place at the Srinivasan Lab, involved a 12-week evaluation using CF-1 mice to model human obesity. GDNF was administered subcutaneously at escalating doses, while semaglutide was given at a standard dosage. The results were striking:

1. **Weight Management**: GDNF reduced weight gain by 10-15% in female mice, achieving a plateau in weight during the final weeks of treatment. In contrast, semaglutide did not produce significant weight loss during the same period.

2. **Glucose Metabolism**: GDNF successfully normalized fasting glucose levels and improved the body’s response to glucose challenges, outperforming semaglutide among female subjects. Improvements were also evident in male models, indicating a broad metabolic advantage.

3. **Liver and Adipose Health**: GDNF led to a 20-30% reduction in liver weight and successfully prevented adipose tissue accumulation in female mice, surpassing the effects seen with semaglutide. This finding suggests GDNF’s potential role in addressing fatty liver disease, a common complication associated with obesity.

According to Robb Knie, CEO of Hoth Therapeutics, “These results are a monumental step forward for Hoth and the fight against obesity. GDNF not only matched but exceeded semaglutide in critical areas, opening doors to a new era of safer, more effective therapies.” He expressed excitement regarding the program’s potential to provide significant benefits for patients and shareholders alike.

Future Directions

The study builds upon previous research indicating GDNF’s protective effects against diet-induced obesity. Future research will focus on liver pathology, lipid content, and gene/protein expression to further clarify GDNF’s mechanisms of action. Hoth Therapeutics aims to accelerate GDNF towards investigational new drug (IND) enabling studies, with a goal of initiating clinical trials in 2027.

Hoth’s GDNF initiative is part of a robust pipeline, which also includes HT-001, currently in Phase 2 for cancer-related skin toxicities; HT-KIT, designated as an orphan drug for mast cell cancers; and HT-ALZ, aimed at treating Alzheimer’s disease.

Hoth Therapeutics is dedicated to developing innovative treatments that address unmet medical needs, focusing on improving patients’ quality of life. As the company moves forward, the implications of these findings could reshape treatment options for obesity and related metabolic disorders globally.